Diisopropylethylamine → HCID 67064719, compound

HRID 1256423Notes

Reaction equation

HRID 1256423 reaction equation
Cl[C:2]1[N:7]2[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[CH:3]=1.[OH:25][CH2:26][CH2:27][NH:28][C:29]([CH:31]1[CH2:36][CH2:35][CH2:34][NH:33][CH2:32]1)=[O:30].C(N(CC)C(C)C)(C)C>CN(C=O)C.CS(C)=O.CO>[OH:25][CH2:26][CH2:27][NH:28][C:29]([CH:31]1[CH2:36][CH2:35][CH2:34][N:33]([C:2]2[N:7]3[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]3[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]3[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=3)[CH:3]=2)[CH2:32]1)=[O:30]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 2760459N-(2-hydroxyethyl)piperidine-3-carboxamideHCID 86652267N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 67064719HCID 67064719, compoundYield 47.3%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2F, 100 mg, 0.290 mmol), N-(2-hydroxyethyl)piperidine-3-carboxamide (100 mg, 0.580 mmol), and N, N-diisopropylethylamine (112 mg, 0.870 mmol) in DMF (1.0 mL) was stirred at 100° C. for 3 h. After cooling to room temperature, the mixture was diluted with a few drops of DMSO and methanol, and was then purified by preparatory HPLC (20-45% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (65.9 mg, 47%). 1H NMR (DMSO-d6) δ: 10.95 (s, 1H), 8.12 (t, J=5.6 Hz, 1H), 7.99 (d, J=8.6 Hz, 2H), 7.61 (d, J=8.6 Hz, 2H), 7.22 (s, 1H), 6.21 (s, 1H), 4.16-4.38 (m, 2H), 3.42-3.51 (m, 1H), 3.40 (t, J=6.2 Hz, 2H), 3.04-3.22 (m, 3H), 2.52-2.63 (m, 1H), 2.38 (s, 3H), 1.86-2.00 (m, 1H), 1.61-1.85 (m, 3H), 1.45 (s, 6H); ESI-MS: m/z 481.2 (M+H)+.

Workup

  1. customwas then purified by preparatory HPLC (20-45% MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-96be9212c77f43e09370199cb732bc50
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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